Cocaine addiction continues to be an important public health problem, with over 2.1 million regular cocaine users in the US. The risks associated with this addiction are enormous and include increased crime and violence as well as increased risk of HIV, and hepatitis. The presence of intravenous cocaine use is one of the strongest predictors for HIV infection, increasing the risk by about four times. Given that there are no effective medication treatments for cocaine addiction, new treatment approaches that will lead to effective treatments are needed. Chronic cocaine use is associated with significant cognitive impairment, which interferes with effective behavioral treatment of this addiction. This proposal will target cognitive function to develop effective treatments for cocaine addiction. We propose to evaluate the effectiveness of a cognitive enhancer, galantamine, for the treatment of cocaine addiction. Galantamine is a cholinesterase inhibitor that is approved for the treatment of Alzheimer's disease. In our pilot studies, galantamine improved attention function in cocaine users and reduced cocaine use. We are proposing a 12-week, double-blind, placebo-controlled, randomized clinical trial. One hundred and twenty cocaine addicted individuals will be randomly assigned one of three treatment groups: placebo, 8 mg/day, or 16 mg/day for galantamine treatment. The main outcome measure will be cocaine use and cognitive performance measures, including measures of attention. We hypothesize that galantamine will be more effective than placebo in reducing cocaine use and improving measures of attention. We also hypothesize that improvement in cocaine use will be mediated by improvement in attention function. This proposal may lead to development of effective treatments for cocaine addiction. PUBLIC HEALTH RELEVANCE: Cocaine addiction continues to be an important public health problem and there are no effective medication treatments for this addiction. This proposed application will test a promising medication, galantamine, for the treatment of cocaine addiction.